Symptoms attributed to alterations in autonomic nerves (autonomic neuropathy) are often observed in diabetes. Since these alterations have not been defined at the biochemical level I propose to investigate the functional state of sympathetic nerves in animal models of diabetes (hereditary diabetes in mice). These studies are relevant to the cardiovascular manifestations of autonomic neuropathy since sympathetic nerves are the prevalent innervation to the heart and peripheral blood vessels. Specifically I propose to investigate the density of sympathetic nerves by measuring the concentration of sympathetic transmitter (norepinephrine) in peripheral organs of diabetic mice. I plan also to examine the functional activity of sympathetic nerves: studies will be performed on the turnover and synthesis rates of norepinephrine, on the levels of synthetic and degrading enzymes for norepinephrine and on parameters of sympathetic synaptic vesicles in the sciatic nerves and the regenerative properties of sympathetic neurones in diabetic mice. These studies will examine sympathetic nerves of mice bearing experimental forms of diabetes which could mimic adult diabetes (obese mice ob-ob strain) and juvenile diabetes (db-db strain).